The objective of this application is to provide funds for the Washington University School of Medicine Drug Abuse Research Center. The center is a multidisciplinary one and consists of a Core Support budget and four individual research elements which address several key biomedical issues in substance abuse. The projects have as their focus the effects of narcotics on the endocrine-hypothalamus. Project 1 examines the effects of opiates on the hypothalamic-pituitary-gonadal axis in the male and probable role of endogenous opioids in this axis; Project 2 is concerned with the neuroanatomical organization of the hypothalamus, particularly with respect to its neuroendocrine function; Project 3 focuses on attempts to utilize excitotoxic amino acids to selectively lesion endogenous opioid-containing pathways in the hypothalamus; and, Project 4 will examine the influence of morphine and diazepam on the neurotoxicity produced by the excitotoxic amino acid, kainic acid. Our center is thus a multidisciplinary one with contributions from both our clinical (psychiatry and pediatrics) and pre-clinical (anatomy and neurobiology) departments. As a final goal of our Research Center, we hope to provide an environment conducive for the training of post-doctoral fellows and the initiation of established investigators into the substance abuse field. Hence, the Washington University School of Medicine Drug Abuse Research Center is both a training and active research center.